Fusidic acid is an antibiotic used to treat skin and soft tissue infections or bone and joint infections caused by gram-positive organisms, including Staphylococcus aureus. Fusidic acid works by interfering with bacterial protein synthesis, specifically by preventing the translocation of elongation factor G1) from the ribosome. The main factors of resistance to fusidic acid are binding site alteration (fusA or fusE=rlpF) or acquired resistance to fusidic acid (fusB, fusC and fusD).
The breakpoint of fusidic acid resistance was 16 μg/ml in this panel. However, fusidic acid MIC values ≥ 2 µg/ml are considered resistant according to the European Committee on Antibiotic Susceptibility Testing (EUCAST) breakpoints. In this study, resistance to fusidic acid was dominant in ST5-MRSA and ST72-MSSA, with the fusA mutation predominant in high resistance. Also, resistance to fusidic acid was common in ST1-MSSA, with fusC acquisition predominant in low resistance.
This study examined the prevalence of resistance to fusidic acid in MSSA and MRSA, stratified by ST and spatype. Fusidic acid is an antibiotic used to treat skin and soft tissue infections or bone and joint infections caused by Gram-positive organisms, including S. aureus6). Recently, fusidic acid-resistant S. aureushas been reported in Europe, North America, Australia, New Zealand, and Taiwan, and the prevalence of fusidic acid resistance ranged from 1.4% to.
Important fusidic acid resistance determinants are alteration of the binding site (fusA or rlpF) or acquired fusidic acid resistance (fusB, fusCand fusD)6). In staphylococci, high-level fusidic acid resistance is usually associated with mutations in fusA encoding EF-G, while low-level resistance is generally caused by the horizontally transferable genes including fusB, fusCand fusD12). In this study, The prevalence of fusidic acid resistance in MSSA and MRSA stratified by ST and spa type was investigated.
Isolation of Bacteria
MLST analyzed the base sequences of seven Staphylococcus aureus housekeeping genes, carbamate kinase (arcC), shikimate dehydrogenase (aroE), glycerol kinase (glpF), guanylate kinase (gmk), phosphate acetyltransferase (pta), triosephotpiome is), acetyl coenzyme A acetyltransferase (star), and determined the MLST sequence type (ST) for each bacterial isolate using the MLST database (http://www.mlst.net). Spa typing is based on sequence analysis of variable number tandem repeats in the gene encoding protein A (Spa) (1). Each new polymorphic repeat base composition found in a strain is assigned a unique repeat code.
In vitro susceptibility to fusidic acid was assessed in triplicate using the reference broth microdilution method as described in the Clinical and Laboratory Standards Institute (CLSI) guidelines. Fusidic acid was dissolved in the specified solvent and added to sterilized Muller-HintonⅡ medium (BD, Franklin Lakes, NJ, USA) to make a mixture with the desired concentration of antibacterial agents. Fusidic acid Minimum Inhibitory Concentration (MIC) values ≥ 2 μg/ml are considered resistant according to the European Committee on Antibiotic Susceptibility Testing (EUCAST) breakpoints.
Mutations in fusA and fusE
Detection of fusidic acid acquired resistance
The present study aimed to determine the prevalence of fusidic acid resistance determinants among 97 MRSA isolates, the entire fusA gene was sequenced and other fusidic acid resistance genes (fusB, fusC and fusD) were detected by PCR. The current study aimed to determine the prevalence of fusidic acid resistance determinants among 109 MSSA isolates, the entire fusAgene was sequenced and other fusidic acid resistance genes (fusB, fusC and fusD) were detected by PCR. In this study, none of the fusidic acid-resistant strains did not show a mutation in fusE.
16spatipes were identified among 90 MRSA isolates resistant to fusidic acid, among which t was the most prevalent type. Proportion of fusidic acid-resistant Staphylococcus aureus stratified by methicillin resistance and sequence type (ST). Prevalence of fusidic acid resistance by bath type in ST5-MRSA and ST5-MSSA isolates.
Prevalence of resistance to fusidic acid by spatype in ST72-MRSA and ST72-MSSA isolates. Prevalence of fusidic acid resistance by spa type in ST1-MSSA and ST513-MSSA isolates. of isolates with resistance to FA classification No. isolates with resistance to FA. aFA, fusidic acid; bND, unspecified. a: CC, clone complex; b: ST, sequence type. In this study, resistance to fusidic acid was common in ST5-MRSA and ST72-MSSA with a predominance of fusAmutation.
Therefore, the rate of fusidic acid resistance in S.aureush had been increased. FusAmutation was the most prevalent fusidic acid resistant mechanism (81%), and acquired fusidic acid resistance was uncommon (29%). However, contrary to our finding, acquired fusidic acid resistance is more common than FusAmutation in Europe 8, 10). In this study, three dominant clones (t127 CC1 MSSA, t002 CC5 MRSA and t688 CC5 MRSA) had fusCgene major clones in fusidic acid resistance S. aureus isolates with low-level resistance, which was similar to that in New Zealand 11). The most common clone was observed to be t2460 ST5-MRSA and all were fusidic acid resistant, while t324 ST72-MRSA was the most common clone but was usually susceptible to fusidic acid.
The most common clone was observed to be t126 ST72-MSSA and all were fusidic acid resistant while t179 ST5-MSSA was the most common clone but usually susceptible to fusidic acid. In conclusion, fusidic acid resistance was common in ST5-MRSA, ST1-MSSA, ST513-MSSA and ST72-MSSA, and rare in ST5-MSSA and ST72-MRSA. These results indicate that most of the strains produced high-level resistance in the L461K of the fusA mutation, which is an important mutation determining the high-level resistance of fusidic acid.
In addition, some spa-type results indicate that in some species fusC is an important factor in determining resistance to low levels of fusidic acid. An epidemic strain of fusidic acid-resistant Staphylococcus aureus carries the fusB determinant, whereas fusA mutations are predominant in other resistant isolates. High use of topical fusidic acid and rapid clonal expansion of fusidic acid-resistant Staphylococcus aureus: a cautionary tale.
결론: 본 연구에서 푸시드산에 대한 내성은 ST5-MRSA와 ST72-MSSA에서 흔했고 ST5-MSSA와 ST72-MRSA에서는 드물었습니다.
